Plasma calcium concentration
mg/dL meq/L mmolL % total
Free ionized 5.0
2.5
1.25
50
Protein-bound 4.2
2.1
1.05
44
Complexed 0.8
0.4
0.2
6
Total
10
5.0
2.50
100
Serum Ca corrections
• Correction of total serum Ca for serum
albumin – add 0.8 meq/L for each 1 gm
reduction in albumin
• Ionized Ca – can obtain if do not have a
serum albumin measurement
• Gadolinium – certain gadolinium salts can
dramatically transiently lower measured
total serum Ca
Hypocalcemia – effects of change
in serum pH
• Alkalosis – decreases ionized Ca
• Acidosis – increases ionized Ca
• Clinical ramifications - if patient is acidotic
and hypocalcemic treatment with NaHCO3
without addressing the hypocalcemia can
further lower ionized Ca
Hypocalcemia – signs and
symptoms
•
•
•
•
•
•
Weakness
Paresthesias
Seizures
Latent tetany – Trousseau, Chvostek signs
Hypotension
Long QT
Tests for latent tetany
• Chvostek sign - tap the skin over the facial
nerve in front of the external auditory
meatus, causes an ipsilateral contraction
of the facial muscles, but up to 10% of
population have a positive test
• Trousseau sign – inflate BP cuff on arm to
20 mmHg>systolic BP for 3-5 min & watch
for carpopedal spasm, insensitive test
Mechanisms of hypocalcemia
• Reduced GI absorption – GI disease,
hypoparathyroidism, vitamin D deficiency
• Renal loss – low Mg, genetic disorders,
drugs (e.g. cisplatinum, cyclosporine,
aminoglycosides, proton pump inhibitors)
• Redistribution of Ca into: bone (post
parathyroidectomy) or abdominal cavity
(pancreatitis)
• Binding by citrate (transfusions) or PO4
load (IV or enema)
Hypocalcemia in critical illness
• Mechanisms:
low Mg
renal failure
blood transfusions (citrate)
multiple mechanisms in gram negative
sepsis including probable cytokine
induction of hypoparathyroidism and
vitamin D deficiency or resistance
• No proof correction of Ca affects course
Hypocalcemia – indications for IV
Ca
• Patients who are severely symptomatic – tetany,
carpopedal spasm, decreased cardiac function,
or prolonged QT interval
• Asymptomatic patients with an acute decrease if
corrected total serum Ca<7.5 mg/dl
• Not an indication - neuromuscular irritability such
as paresthesias and corrected total serum
Ca >7.5; initial treatment with oral Ca sufficient
Hypocalcemia treatment with bolus
intravenous Ca
• Calcium gluconate – 10 mL of a 10% solution is
90 mg of elemental Ca
• Calcium chloride – 10 mL of a 10% solution is
270 mg of elemental Ca
• Tissue necrosis with extravasation – much more
common with calcium chloride
• Code cart – contains Ca chloride
• Formation of insoluble Ca salts – occurs when
HCO3 or PO4 is added to solution containing Ca
• Hyperkalemia with marked EKG changes (with
no hypocalcemia) – affects conduction not
serum [K+]
Hypocalcemia Rx with Ca infusion
• Since duration of action of IV Ca bolus is
just 1-3 hours to maintain the serum Ca
level may need to give IV infusion
• Add 11 amps of Ca gluconate to either
D5W or NS to make a 1 L solution with a
Ca concentration of 1 mg/ml
• Usual starting rate 1 ml/minute or
60 mg/hour of elemental Ca
Hypocalcemia with concurrent
hypomagnesemia
• Often cannot correct the Ca unless the Mg is
corrected
• Give 2 gm of Mg (16 meq) of MgSO4 as a 10%
solution over 10 to 20 minutes
• Followed by 1 gm MgSO4 (8 meq) at 100 mL/hr
• Continue intravenous MgSO4 as long as Mg < 1
mg/dL
• Careful monitoring if patient has impaired renal
function
Vitamin D nomenclature
• Vitamin D – cholecalciferol D3,
ergocalciferol D2
• 25-hydroxy vitamin D - calcidiol D3,
ercalcidiol D2
• Vitamin D receptor agonist - calcitriol D3
(Rocaltrol), paricalcitol D2 (Zemplar) a
synthetic analog, doxercalciferol D2
(Hectoral) a synthetic prohormone
Measurement of vitamin D
deficiency or insufficiency
• Vitamin D deficiency best determined by
measuring 25-OH vitamin D even though the
active form is 1,25 dihydroxy vitamin D
• This is because 1,25 dihydroxy vitamin D levels
are often normal in vitamin D insufficiency
because of a compensatory increase of PTH
which then stimulates conversion of 25 to 1,25
dihydroxy vit D
• 25-hydroxy vitamin D levels are reported as a
combination of D2 and D3
• Vitamin D deficiency < 20 ng/ml
• Vitamin D insufficiency 20-30 ng/ml
Sources of vitamin D
• Very few foods contain vitamin D (livers of fatty fish are
the exception)
• Synthesis in the skin of vitamin D3 during exposure to
UV rays in sunlight is a major source
• This system is exceedingly efficient and brief casual
exposure such as 10-15 minutes of the arms and face is
equivalent to ingestion of 200 IU per day
• Disabled persons and elderly may have inadequate sun
exposure
• Skin of those >70 does not convert vitamin D effectively
• At northern latitudes there is not enough radiation to
convert vitamin D, particularly during the winter
Vitamin D deficiency
• Elderly – up to 74% deficient in vitamin D
even if adequate intake; suggested
guidelines in elderly 800-1000 IU/day
• NHANES study – 42% of African American
women were deficient vs 4% Caucasian
• Response to bisphosphonates – may be
blunted if vitamin D deficient
Hypocalcemia – rationale for Rx
with calcitriol (Rocaltrol)
• PTH stimulates the conversion of 25-hydroxy
vitamin D to 1-25 dihydroxy vitamin D
• So if give a patient with hypoparathyroidism
vitamin D it would not be converted to the active
form 1-25 dihydroxy vitamin D (calcitriol)
• Calcitriol must be given in this circumstance.
• Onset of action – much quicker in onset than
vitamin D which may take several days
• Offset of action – much quicker than vitamin D,
so if develop hypercalcemia of shorter duration
• Dosage - start with .25 ug bid, up to 2 ug per day
• Elevated urinary Ca and nephrolithiasis – can be
induced by calcitriol even if no hypercalcemia
Ergocalciferol vs cholecalciferol
• Vitamin D2 – ergocalciferol (nephrologists
use since listed in their guidelines)
• Vitamin D3 - cholecalciferol, longer halflife, greater activity
Vitamin D dosage in Rx of chronic
hypocalcemia
Simple dietary deficiency - can be corrected by
the use of ergocalciferol 400-2000 IU/day
• However in conjunction with other hypocalcemic
disorders (e.g., underlying impairments in
vitamin D metabolism or renal insufficiency)
larger doses may be needed e.g., a 6 to 8 week
regimen of 50,000 units, dosed weekly
• Severe malnutrition or malabsorption – may
require even higher doses
Oral calcium supplements
• Calcium carbonate - 40% elemental Ca
(Oscal 250 or 500 mg Ca per tablet or
Tums ES 400 mg Ca per tablet)
• Calcium acetate - 25% elemental Ca
(Phoslo)
• Calcium Citrate 21% elemental Ca
(Citracal)
• Dose – 1-2 gm of elemental calcium tid
• Should give apart from meals to enhance
Ca absorption
Symptoms of severe phosphate
depletion (< 1mg/dl)
• In general are due to inability to form ATP
as well as impaired oxygen delivery due to
a decrease in RBC 2,3 DPG:
1) muscle injury - rhabdomyolysis,
impaired diaphragmatic function, CHF
2) neurologic - paresthesias, dysarthria,
confusion, stupor, seizures, coma
3) hematologic (rare) – hemolysis,
thrombocytopenia
Hypophosphatemia treatment
• Acute moderate hypophosphatemia
(1-2.5 mg/dl) - is common in hospitalized
patients, often due to transcellular shifts, if
asymptomatic may require no treatment
except correction of underlying cause
• Acute severe hypophosphatemia
(< 1 mg/dl) - may require intravenous P if
serious clinical manifestations
Intravenous phosphorus treatment
for hypophosphatemia
• Total body P deficit – can not be easily
determined but has been demonstrated that the
dosage listed below can be given safely
• Infuse 0.08 to 0.16 mmol/kg in 500 mL of .45%
NS over 6 hours and stop when P>1.5 mg/dl (so
in a 100 kg patient this is 8-16 mm - order set in
Cerner is for 10 mm)
• Duration of infusion – it may take 24-48 hours to
replenish intracellular stores
• Hypocalcemia is the main risk (binding of serum
Ca by the P) especially with prolonged infusions;
hyperphosphatemia
Phosphorus preparations
• Normal dietary P about 1000 mg
• 1 mmol P = 31 mg
• Neutraphos - 250 mg elemental P, K+ 7 meq, Na+ 7
meq
• Neutra-Phos potassium - 250 mg elemental P, K+ 14
meq
• Fleets Phospho-Soda – 815 mg P, Na+ 33 meq/ 5 mls
• Intravenous K+ phosphate – 1.5 meq KCl/mm PO4
• Intravenous Na+ phosphate - 1.3 meq NaCl/mm PO4
• Intravenous phosphate preparations recently not always
available in hospital pharmacies
Hypomagnesemia - signs and
symptoms
• Nonspecific symptoms – anorexia,
nausea, apathy
• Hypocalcemia – tetany, seizures, positive
Chvostek and Trousseau signs
• Hypokalemia – weakness, arrhythmias
• Increased susceptibility to ventricular
arrhythmias during myocardial ischemia
Significance of low serum Mg in CV
disease
• Mild hypomagnesemia is common with diuretics
• Predisposes to cardiac arrhythmias in the
settings of acute ischemic event, CHF,
cardiopulmonary bypass, torsades de pointes, or
in ICU patients
• Myocardial infarction - with low Mg is increased
risk of ventricular arrhythmias especially first 24
hours - which risk may be reduced by IV Mg
• Torsades de pointes – increased risk with low
Mg especially if on class Ia or III antiarrhythmics
Plasma magnesium concentration
mg/dL meq/L
Free
1.3
1.1
Complexed
0.4
0.32
Protein-bound 0.4
0.32
Total
2.1
1.76
(1.9-2.3) (1.5-2.0)
mmolL
0.55
0.16
0.16
0.87
(0.7-1.0)
Hypomagnesemia treatment
• Severe symptomatic hypomagnesemia
(tetany, hypocalcemia, arrhythmias): treat
intravenously: e.g., 50 meq IV over 8 to 24
hours, to maintain Mg >1 mg/dl
• MgSO4 vial =1 gm MgSO4=96 mg
elemental Mg=8 meq
• Asymptomatic hypomagnesemia: treat
with oral agents
Oral magnesium preparations
• Normal daily dietary Mg intake 360 mg
• Mag-Ox 400 - 240 mg of elemental Mg per 400
mg tablet
• Uro-Mag – 84 mg per 140 mg tablet
• Sustained release (Slow-Mag) - 64 mg per tablet
• Typically 240 mg of elemental Mg is given for
dietary deficiency, more severe deficiency may
require up to 720 mg/day elemental Mg
• major side effect - diarrhea
Hypermagnesemia
• Urinary Mg excretion can increase more
than fivefold in response to a Mg load thus
hypermagnesemia is typically only seen in
the setting of renal failure when a very
large Mg load is given intravenous, oral,
via enema
Hypermagnesemia - clinical
manifestations
• Mg 4-6 meq/L – lethargy, drowsiness,
diminished reflexes
• Mg 6-10 meq/L – somnolence,
hypocalcemia, absent reflexes, low BP,
bradycardia, EKG changes (with IV Mg in
eclampsia usual level 5-7 meq/L)
• Mg >10 meq/L – muscle paralysis,
complete heart block, cardiac arrest
Hypermagnesemia – signs and
symptoms
• 3 types of symptoms are seen when Mg
>4 meq/L :
1) neuromuscular effects (curare like)
2) cardiovascular effects
(Ca and K channel blockade)
3) hypocalcemia (PTH suppression)
Hypermagnesemia – treatment of
symptomatic patient
• If renal function is normal cessation of Mg
allows prompt restoration of normal levels
• If renal function is impaired hemodialysis
is effective in removing Mg
• In cases with severe symptoms 100-200
mg elemental Ca over 5-10 minutes is
effective antagonist
Key points
• Main risk of IV Mg is giving to azotemia patients
and development of hypermagnesemia
• Main risk of IV P is binding to serum Ca causing
hypocalcemia, usually with prolonged infusions
not adequately followed
• Main risk of IV Ca - infiltration of vein and tissue
necrosis, especially with calcium chloride
• If hypocalcemia consider may also be low [Mg]
• If hypokalemia consider may also be low [Mg]
• Hypermagnesemia – inhibit effects with IV Ca